PMID- 28315324 OWN - NLM STAT- MEDLINE DCOM- 20170605 LR - 20231213 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 486 IP - 2 DP - 2017 Apr 29 TI - Nucleolin protects macrophages from oxLDL-induced foam cell formation through up-regulating ABCA1 expression. PG - 364-371 LID - S0006-291X(17)30505-3 [pii] LID - 10.1016/j.bbrc.2017.03.047 [doi] AB - Our recent studies have indicated that nucleolin, as a multifunctional RNA-binding protein, exerts protective effects in the myocardial cells and endothelial cells under the condition of oxidative stress. However, the function of nucleolin and its potential mechanism in macrophage-derived foam cell formation remain largely unexplored. ApoE-/- mice were fed with a high-fat diet (HFD) for 10-24 weeks. Protein expression was measured by western blotting or immunofluorescence, and gene expression at the mRNA level was detected by qRT-PCR. The level of lipid in macrophages was examined by Oil Red O staining, high-performance liquid chromatography (HPLC) and NBD-cholesterol. Actinomycin D (Act D) was used to determine the stability of ABCA1 mRNA in macrophages. The interaction of nucleolin with ABCA1 mRNA was assessed using co-immunoprecipitation (co-IP). The aortas advanced plaques demonstrated significantly lower levels of nucleolin protein compared with early plaques in ApoE-/- mice, in which the macrophage foam cells occupied main body. Nucleolin expression at the mRNA and protein levels in RAW264.7 macrophages was significantly reduced by oxidized low-density lipoprotein (oxLDL) in a dose- and time-dependent manner. Furthermore, nucleolin overexpression markedly attenuated lipid accumulation in oxLDL-challenged macrophages through increasing cholesterol efflux. In addition, nucleolin overexpression significantly increased the expression of ATP-binding cassette transporter A1 (ABCA1) at the mRNA and protein levels without affecting expressions of scavenger receptors (SR)-A, SR-B1, CD36 and ATP-binding cassette transporter G1 (ABCG1) at the mRNA level. Moreover, nucleolin overexpression increased the stability of ABCA1 mRNA in macrophages, whereas nucleolin ablation abrogated the oxLDL-induced up-regulation of ABCA1. The up-regulation of ABCA1 by nucleolin resulted from its protein-RNA interaction. Our data suggested that nucleolin inhibited foam cell formation through enhancing stability of ABCA1 mRNA and subsequently increasing cholesterol efflux. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Li, Yuanbin AU - Li Y AD - Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, PR China. FAU - Jiang, Bimei AU - Jiang B AD - Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, PR China. Electronic address: jiangbimei@163.com. FAU - Liang, Pengfei AU - Liang P AD - Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China. FAU - Tong, Zhongyi AU - Tong Z AD - Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, PR China. FAU - Liu, Meidong AU - Liu M AD - Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, PR China. FAU - Lv, Qinglan AU - Lv Q AD - Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, PR China. FAU - Liu, Yanjuan AU - Liu Y AD - Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, PR China. FAU - Liu, Xuanyou AU - Liu X AD - Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, PR China. FAU - Tang, Yuting AU - Tang Y AD - Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, PR China. FAU - Xiao, Xianzhong AU - Xiao X AD - Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, PR China. LA - eng PT - Journal Article DEP - 20170314 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (ABCA1 protein, mouse) RN - 0 (ABCG1 protein, mouse) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (Apolipoproteins E) RN - 0 (CD36 Antigens) RN - 0 (Lipoproteins, LDL) RN - 0 (Phosphoproteins) RN - 0 (RNA, Messenger) RN - 0 (RNA-Binding Proteins) RN - 0 (Scarb1 protein, mouse) RN - 0 (Scavenger Receptors, Class A) RN - 0 (Scavenger Receptors, Class B) RN - 0 (oxidized low density lipoprotein) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - ATP Binding Cassette Transporter 1/*genetics/metabolism MH - ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics/metabolism MH - Animals MH - Apolipoproteins E/deficiency/genetics MH - Atherosclerosis/etiology/*genetics/metabolism/pathology MH - Biological Transport/drug effects MH - CD36 Antigens/genetics/metabolism MH - Cell Differentiation MH - Cell Line MH - Cholesterol/metabolism MH - Diet, High-Fat MH - Dose-Response Relationship, Drug MH - Foam Cells/drug effects/metabolism/pathology MH - Gene Expression Regulation MH - Hyperlipidemias/etiology/*genetics/metabolism/pathology MH - Lipoproteins, LDL/*pharmacology MH - Macrophages/drug effects/metabolism/pathology MH - Male MH - Mice MH - Mice, Knockout MH - Phosphoproteins/*genetics/metabolism MH - RNA Stability MH - RNA, Messenger/*genetics/metabolism MH - RNA-Binding Proteins/*genetics/metabolism MH - Scavenger Receptors, Class A/genetics/metabolism MH - Scavenger Receptors, Class B/genetics/metabolism MH - Signal Transduction MH - Nucleolin OTO - NOTNLM OT - ABCA1 OT - Atherosclerosis OT - Lipoprotein OT - Nucleolin OT - mRNA stability EDAT- 2017/03/21 06:00 MHDA- 2017/06/06 06:00 CRDT- 2017/03/19 06:00 PHST- 2017/02/24 00:00 [received] PHST- 2017/03/13 00:00 [accepted] PHST- 2017/03/21 06:00 [pubmed] PHST- 2017/06/06 06:00 [medline] PHST- 2017/03/19 06:00 [entrez] AID - S0006-291X(17)30505-3 [pii] AID - 10.1016/j.bbrc.2017.03.047 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2017 Apr 29;486(2):364-371. doi: 10.1016/j.bbrc.2017.03.047. Epub 2017 Mar 14.